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Published on: December 16, 2021
Microbiota in mesenteric adipose tissue from Crohn's disease promote colitis in mice
Zhen He1,2, Jinjie Wu1,2, Junli Gong1,2
1Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.
Background:
Mesenteric adipose tissue (mAT) hyperplasia, known as creeping fat is a pathologic characteristic of Crohn's disease (CD). The reserve of creeping fat in surgery is associated with poor prognosis of CD patients, but the mechanism remains unknown.
Methods:
Mesenteric microbiome, metabolome, and host transcriptome were characterized using a cohort of 48 patients with CD and 16 non-CD controls. Multidimensional data including 16S ribosomal RNA gene sequencing (16S rRNA), host RNA sequencing, and metabolome were integrated to reveal network interaction. Mesenteric resident bacteria were isolated from mAT and functionally investigated both in the dextran sulfate sodium (DSS) model and in the Il10 gene-deficient (Il10-/-) mouse colitis model to validate their pro-inflammatory roles.
Results:
Mesenteric microbiota contributed to aberrant metabolites production and transcripts in mATs from patients with CD. The presence of mAT resident microbiota was associated with the development of CD. Achromobacter pulmonis (A. pulmonis) isolated from CD mAT could translocate to mAT and exacerbate both DSS-induced and Il10 gene-deficient (Il10-/-) spontaneous colitis in mice. The levels of A. pulmonis in both mAT and mucous layer from CD patients were higher compared to those from the non-CD group.
Conclusions:
This study suggests that the mesenteric microbiota from patients with CD sculpt a detrimental microenvironment and promote intestinal inflammation. Video abstract.
Insights
Mesenteric resident bacteria in Crohn's disease (CD) patients promote intestinal inflammation. The bacterium Achromobacter pulmonis was found to exacerbate colitis in mouse models, suggesting a role in CD pathogenesis.
Area of Science:
- Gastroenterology
- Microbiology
- Immunology
Background:
- Crohn's disease (CD) is characterized by mesenteric adipose tissue (mAT) hyperplasia, termed creeping fat.
- The prognostic significance of creeping fat in CD surgery is known, but the underlying mechanisms are unclear.
Purpose of the Study:
- To investigate the role of mesenteric microbiota in the pathogenesis of Crohn's disease.
- To identify specific bacteria within mAT that contribute to intestinal inflammation.
Main Methods:
- Integrated analysis of mesenteric microbiome, metabolome, and host transcriptome in CD patients and controls.
- 16S rRNA sequencing, host RNA sequencing, and metabolomics were employed.
- Isolation and functional validation of mAT resident bacteria in mouse colitis models (DSS and Il10-/-).
Main Results:
- Mesenteric microbiota in CD patients contribute to aberrant metabolites and transcripts in mAT.
- The presence of mAT resident microbiota is linked to CD development.
- Achromobacter pulmonis (A. pulmonis) isolated from CD mAT translocated and worsened colitis in mice, with higher levels observed in CD patients.
Conclusions:
- Mesenteric microbiota in CD patients create a harmful microenvironment that promotes intestinal inflammation.
- A. pulmonis may play a significant role in the inflammatory processes of Crohn's disease.

